A RANDOMIZED NON-COMPARATIVE PHASE 2 PILOT STUDY TESTING THE VALUE OF IMATINIB MESYLATE AS AN EARLY TREATMENT OF COVID-19 DISEASE IN AGED HOSPITALIZED PATIENTS.
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 99
- 试验地点
- 2
- 主要终点
- To evaluate the benefit of early imatinib therapy to prevent severe COVID-19 disease in hospitalized aged patients.
研究概览
简要总结
High-throughput screening studies identified Abl kinase inhibitors (including imatinib) as inhibitors of coronaviruses SARS and MERS. The SARS-CoV-2 coronavirus depend on Abl2 kinase activity to fuse and enter into the cells. Pharmacokinetic studies demonstrated that IC50 of imatinib for ABL1, BCR-ABL1 and ABL2 kinase inhibition is less than 1 microM (around 0.3 microM) below the expected trough plasmatic concentrations of imatinib 400 mg/day (1.7 microM). The EC50 of imatinib for the inhibition of the virus is under investigation but we now have a first estimates with EC50 close to 2.5 microM. This plasmatic concentration is achievable with imatinib 800 mg/d. We hypothesize that clinically achievable imatinib concentration will block the first round of cell to cell virus infection and therefore stop or prevent from SARS-CoV-2 infection in human. Based on our 20 years' experience of prescribing imatinib in patients, we expect that most of the adverse events and pharmacological interactions of imatinib can be anticipated and corrected. The eligible population will be aged (>70y) patients hospitalized for a non-severe COVID-19 disease for less than 7 days. Patients will be randomized 1/1 between standard of care and imatinib 800 mg per day during 14 days. The primary endpoint will be the death rate by 30 days. Secondary endpoint will include progression to severe CIVID-19 disease, safety, outcome at 3 months. We plan to randomize 90 patients in order to show a 10% benefit in term of death rate reduction from 16% to 6%.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 70 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •. Patient aged > 70y
- •Patient with a documented COVID-19 disease by SARS-CoV-2 RT-PCR (if no test is available, suspected COVID-19 disease on CT SCAN).
- •Initial phase (≤ 7 days) of COVID-19 disease
- •Non severe COVID-19 disease
- •Signed informe consent
排除标准
- •Patient in palliative care
- •Severe COVID-19 disease (SpO2 ≤ 94% with O2 ≥ 5 l/min)
- •Contra-indication to imatinib
- •Therapy with Warfarin (Heparin allowed)
- •Stage II to IV congestive heart failure (CHF) as determined by the New York Heart Association (NYHA)
- •Peripheral edema grade > 2
- •Known HBV, HBC or HIV infection
- •Known hepatic failure
- •Patient under legal protection
研究组 & 干预措施
Expérimental ARM
800mg/d IMATINIB during 14days
干预措施: Experimental drug (Drug)
结局指标
主要结局
To evaluate the benefit of early imatinib therapy to prevent severe COVID-19 disease in hospitalized aged patients.
时间窗: 30 days
To evaluate the 30 days mortality rate in aged patients hospitalized with COVID-19
次要结局
- To evaluate plasmatic levels of imatinib(14 days)
- To evaluate mortality(90 days)
- To evaluate viral load(14 days)
- To evaluate the feasibility of imatinib therapy.(Day 14)
- To evaluate safety of imatinib therapy(3 months)
- To evaluate the clinical evolution(3 months)
- To evaluate the progression rate to severe COVID-19 disease(3 months)
研究者
Philippe ROUSSELOT
MD
Versailles Hospital